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Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
by
Lombardi, Francesca
, Cifone, Maria Grazia
, Ciafarone, Alessia
, Augello, Francesca Rosaria
, Latella, Giovanni
, Palumbo, Paola
, Cinque, Benedetta
, Artone, Serena
in
Adalimumab - pharmacology
/ Anti-Inflammatory Agents - pharmacology
/ Azathioprine - pharmacology
/ Budesonide - pharmacology
/ Caco-2 Cells
/ Cell Differentiation - drug effects
/ Cells
/ Collagen
/ Drug dosages
/ Epithelial-Mesenchymal Transition - drug effects
/ Fibroblasts
/ Fibrosis
/ Humans
/ Inflammation
/ Inflammatory bowel disease
/ Inflammatory Bowel Diseases - drug therapy
/ Inflammatory Bowel Diseases - metabolism
/ Inflammatory Bowel Diseases - pathology
/ Infliximab - pharmacology
/ Infliximab - therapeutic use
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestines - drug effects
/ Intestines - pathology
/ Kinases
/ Mesalamine - pharmacology
/ Methotrexate - pharmacology
/ Methylprednisolone - pharmacology
/ Monoclonal antibodies
/ Myofibroblasts - drug effects
/ Myofibroblasts - metabolism
/ Prednisone - pharmacology
/ Proteins
/ Smooth muscle
/ Transforming Growth Factor beta1 - metabolism
/ Tumor necrosis factor-TNF
2024
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Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
by
Lombardi, Francesca
, Cifone, Maria Grazia
, Ciafarone, Alessia
, Augello, Francesca Rosaria
, Latella, Giovanni
, Palumbo, Paola
, Cinque, Benedetta
, Artone, Serena
in
Adalimumab - pharmacology
/ Anti-Inflammatory Agents - pharmacology
/ Azathioprine - pharmacology
/ Budesonide - pharmacology
/ Caco-2 Cells
/ Cell Differentiation - drug effects
/ Cells
/ Collagen
/ Drug dosages
/ Epithelial-Mesenchymal Transition - drug effects
/ Fibroblasts
/ Fibrosis
/ Humans
/ Inflammation
/ Inflammatory bowel disease
/ Inflammatory Bowel Diseases - drug therapy
/ Inflammatory Bowel Diseases - metabolism
/ Inflammatory Bowel Diseases - pathology
/ Infliximab - pharmacology
/ Infliximab - therapeutic use
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestines - drug effects
/ Intestines - pathology
/ Kinases
/ Mesalamine - pharmacology
/ Methotrexate - pharmacology
/ Methylprednisolone - pharmacology
/ Monoclonal antibodies
/ Myofibroblasts - drug effects
/ Myofibroblasts - metabolism
/ Prednisone - pharmacology
/ Proteins
/ Smooth muscle
/ Transforming Growth Factor beta1 - metabolism
/ Tumor necrosis factor-TNF
2024
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Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
by
Lombardi, Francesca
, Cifone, Maria Grazia
, Ciafarone, Alessia
, Augello, Francesca Rosaria
, Latella, Giovanni
, Palumbo, Paola
, Cinque, Benedetta
, Artone, Serena
in
Adalimumab - pharmacology
/ Anti-Inflammatory Agents - pharmacology
/ Azathioprine - pharmacology
/ Budesonide - pharmacology
/ Caco-2 Cells
/ Cell Differentiation - drug effects
/ Cells
/ Collagen
/ Drug dosages
/ Epithelial-Mesenchymal Transition - drug effects
/ Fibroblasts
/ Fibrosis
/ Humans
/ Inflammation
/ Inflammatory bowel disease
/ Inflammatory Bowel Diseases - drug therapy
/ Inflammatory Bowel Diseases - metabolism
/ Inflammatory Bowel Diseases - pathology
/ Infliximab - pharmacology
/ Infliximab - therapeutic use
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestines - drug effects
/ Intestines - pathology
/ Kinases
/ Mesalamine - pharmacology
/ Methotrexate - pharmacology
/ Methylprednisolone - pharmacology
/ Monoclonal antibodies
/ Myofibroblasts - drug effects
/ Myofibroblasts - metabolism
/ Prednisone - pharmacology
/ Proteins
/ Smooth muscle
/ Transforming Growth Factor beta1 - metabolism
/ Tumor necrosis factor-TNF
2024
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Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
Journal Article
Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
2024
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Overview
The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.
Publisher
MDPI AG,MDPI
Subject
/ Anti-Inflammatory Agents - pharmacology
/ Cell Differentiation - drug effects
/ Cells
/ Collagen
/ Epithelial-Mesenchymal Transition - drug effects
/ Fibrosis
/ Humans
/ Inflammatory Bowel Diseases - drug therapy
/ Inflammatory Bowel Diseases - metabolism
/ Inflammatory Bowel Diseases - pathology
/ Infliximab - therapeutic use
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Kinases
/ Methylprednisolone - pharmacology
/ Myofibroblasts - drug effects
/ Proteins
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